Our long term goal is directed at gaining a more complete understanding of how thymus dependent (T) and thymus independent (B) lymphocytes interact in producing a specific immune response to antigen. More specifically, we feel that the mounting evidence suggesting that T-cells act as regulators of immune responsiveness makes it of particular interest to clarify the nature of the T-cell interaction with antigen. Toward this end we plan to focus our immediate attentions on developing methods for the rapid identification and isolation of functional antigen-binding cells. Using enriched populations we will be better equipped to characterize this subset of T-cells with regard to maturational stage, surface antigenic markers, and relative abilities to participate in other known T-dependent functions. In addition, it will become possible to follow, biochemically and cytologically, the cellular changes triggered by antigen on reactive T-cells, and to compare these changes in cells from tolerant and immune animals. We felt that the ability to detect, quantify, and isolate specific antigen-binding T-cells will provide a means of analyzing more completely the T-cell mediated regulatory events that determine whether the response to antigen will be positive (immunity) or negative (tolerance or suppression). Comparative studies of the T-cell's ability to recognize and respond to antigen in normal, immune and tolerant or suppressed animals will be our primary research interest over the period of this grant. BIBILIOGRAPHIC REFERENCES: Stout, R.D., Waksal, S.D., Sato, V.L., Okumura, K., and Herzenberg, L.A. In Leukocyte Membrane Determinants Regulating Immune Reactivity, V.P. Eijsorogel, Ed. (1976). Herzenberg, L.A., Okumura, K., Cantor, H., Sato, V.L., Bryse, E.A., Shen, F.W. (1976) The cellular basis of allotype suppression: demonstration of allotype specific helper T-cells and their removal by suppressor T cells. J. Exp. Med. 144, 330.